The goals of this research proposal are to delineate the mechanisms of the development of cell-mediated hypersensitivity in man. The importance of the lymphocyte in the expression of cell-mediated reactions is well documented but complex interactions are known to take place between the several populations of lymphocytes, including the "B" and "T" lymphocytes. Fractionation and purification of these heterogeneous lymphoid cell populations is mandatory for a better understanding of the role of these cells in hypersensitivity phenomena. the several populations of human lymphocytes will be separated on the basis of their surface antigenic receptors or their surface immunoglobulins reacting with its specific antigen or antibody coated onto plastic beads or nylon fibers. The reacting lymphocytes will be retained on an appropriately constructed column or matrix. These several populations of lymphocytes will then be utilized in developing adequate in vitro detection systems for the quantification of cell- mediated hypersensitivity, one of the most important current needs of immunologists. This methodology will be applied to the study of the ontogeny of cell mediated hypersensitivity; these studies will include not only the fetal and neonatal development, but will be extended to include mature adult progressing into senescence. Studies will also include the biologic, chemical and immunologic characterization of the effector molecules involved in the mediation of cellular immunity, including migration inhibition factor, cytotoxicity factors and transfer factor. It is anticipated that these studies will have considerable application in better understanding those immunologic diseases, in which cell mediated hypersensitivity develops or doesn't develop to allergens, contactants, drugs, homografts, bacteria, viruses and tumors.